Nuclear, Biologic, & Chemical Agents; Weapons of Mass Destruction: Introduction
For centuries, military forces have utilized nonconventional weapons using various chemical and biologic agents. During World War I, powerful chemical weapons were developed that affected hundreds of thousands of soldiers. Nuclear weapons were first created during World War II with devastating results. Today, thousands of these nuclear, biologic, and chemical weapons of mass destruction are stored in facilities throughout the world. An accident at any of these facilities could result in a large number of civilian casualties. In addition, many terrorist organizations are now actively attempting to purchase, steal, or develop such weapons for their use. As with most mass casualty situations, emergency physicians will be at the forefront of patient care. This chapter attempts to provide specific information regarding the management of nuclear, biologic, and chemical weapons injuries.
Nuclear Weapons
A terrorist attack utilizing a nuclear weapon would most likely involve the detonation of a nuclear bomb or the detonation of a conventional explosive that also dispersed radioactive material (so-called dirty bomb).
The detonation of a nuclear weapon results in a much larger blast area and much hotter fireball than that produced by conventional explosives. If victims survive the blast trauma and thermal burns, they are at risk for radiation injuries. There are four types of radioactive particles that may cause damage when they interact with body tissue:
Alpha particles are large particles that are stopped by the epidermis and cause no significant external damage. Internal contamination, from the inhalation or ingestion of contaminated particles, may cause local tissue injury.
Beta particles are small particles that can penetrate the superficial skin and cause mild-burn-type injuries.
Gamma rays are high-energy particles that can enter tissues easily and cause significant damage to multiple body systems.
Neutrons are large particles that are typically produced only during nuclear detonation. Like gamma rays, they cause significant tissue injury.
The effect that radiation will have on the body depends on the type of radiation, the amount of exposure, and the body system involved. Tissues that display higher rates of cellular mitosis, such as the gastrointestinal and hematopoietic systems, are more severely affected. At very high radiation doses, neurovascular effects will also be seen. Radiation injury may cause either abnormal cell function or cell death.
The symptoms and signs of radiation exposure occur in three phases: prodromal, latent, and symptomatic.
Patients will develop nonspecific symptoms of nausea, vomiting, weakness, and fatigue. Symptoms generally last no longer than 24–48 hours. With higher radiation exposures, symptoms will occur earlier and last longer.
The latent period duration depends on the dose of radiation and the body system involved (neurologic, several hours; gastrointestinal, 1–7 days; hematopoietic, 2–6 weeks).
Symptoms will depend largely on the body system affected, which will depend on the radiation dose. At doses of 0.7–4 Gy, the hematopoietic system will begin to manifest signs and symptoms of bone marrow suppression. Because of their long life span, erythrocytes are less severely affected than are the myeloid and platelet cell lines. Neutropenia and thrombocytopenia may be significant and lead to infectious and hemorrhagic complications. At doses of 6–8 Gy, gastrointestinal symptoms develop. Nausea, vomiting, diarrhea (bloody), and severe fluid and electrolyte imbalances will occur. The neurovascular system becomes affected at doses of 20–40 Gy. Symptoms include headache, mental status changes, hypotension, focal neurologic changes, convulsions, and coma. Exposures in this range are uniformly fatal.
Obtain a complete blood count with differential for all patients sustaining a radiation injury. Although symptomatic bone marrow suppression may not be evident for some weeks, a drop of the absolute lymphocyte count of 50% at 24–48 hours is indicative of significant exposure. Monitor electrolytes in patients with gastrointestinal symptoms.
In the absence of aggressive medical therapy, the LD50 (the dose of radiation that will kill 50% of those exposed) is approximately 3.5 Gy. Aggressive medical care affords improved survival. Treat all life-threatening injuries associated with blast or thermal effects according to standard advanced trauma life support protocols. Perform surgical procedures early to avoid the electrolyte and hematopoietic effects that will occur. Clean wounds extensively and close them as soon as possible to prevent infection. Treat nausea and vomiting with standard antiemetic medications (prochlorperazine, promethazine, ondansetron). Treat fluid and electrolyte abnormalities with appropriate replacement. Anemia and thrombocytopenia can be treated with transfusion therapy. Leukopenia may be treated with hematopoietic growth factors such as sargramostim and filgrastim. In some instances, bone marrow transplantation may be utilized. Follow neutropenic precautions at absolute neutrophil counts below 500. Some authors recommend prophylactic antibiotics at counts below 100. Use broad-spectrum antibiotics to treat infections. Infection is the most common cause of death in radiation patients.
Remove all contaminated clothing. Change contaminated dressings and splints. Thoroughly clean the patient’s skin with soap and water or a 0.5% hypochlorite solution. Hair should be washed and in some instances removed. Eyes may be washed with large amounts of water or sterile saline. All contaminated materials should be bagged if possible and sent for proper disposal.
Patients who have been decontaminated and have only mild transient symptoms can be safely discharged. Because of the variable and lengthy latent period involved with this disorder, early admission is not indicated. Patients should be closely monitored and admitted when warranted.
Biologic Weapons
Many agents may be used as biologic weapons. The most likely pathogens are presented here. Biologic agents can be classified as bacterial agents, viral agents, and biologic toxins. A high index of suspicion will be required in order to identify patients who have experienced a biologic attack. A large number of patients with severe febrile illnesses will be the most likely clue. Keep in mind that the attack most likely occurs by aerosol release of infectious material several days prior to patient presentation.
See Table 3–1.
| Agent | Syndrome | Incubation | Symptoms | Treatmenta | ||
|---|---|---|---|---|---|---|
| Early | Late | First-Line | Prophylaxis | |||
| Anthrax (Bacillus anthracosis; gram-positive, sporulating) | Inhalational | 1–7 d | Fever, chills, nausea and vomiting, headache, cough, dyspnea, chest pain, abdominal pain | High fever, diaphoresis, cyanosis, hypotension, lymphadenopathy, shock, death (within 3 d of late symptom onset) | Ciprofloxacin, 400 mg IV q 12 h, or doxycycline, 200 mg IV, and then 100 mg IV q 12 h. Without use of vaccine, treat for 60 days; with use of vaccine, treat for 30 days. As patient improves, may begin oral therapy | Ciprofloxacin, 500 mg PO b.i.d. × 1 wk, or doxycycline, 100 mg PO b.i.d. × 4 wk and begin vaccine |
| Gastrointestinal (upper) | Oral or esophageal ulcer | Regional lymphadenopathy, sepsis | ||||
| Gastrointestinal (lower) | Nausea and vomiting, diarrhea (bloody) | Acute abdomen, sepsis | ||||
| Cutaneous | 2 d | Pruritic papule → ulcer → vesicle → painless eschar | Regional lymphadenopathy, occasional sepsis (1–2 wk after onset) | |||
| Plague (Yersinia pestis; gram-negative bacillus) | Bubonic | 1–7 d | Fever, chills, malaise, lymphadenopathy | Necrotic lymphadenitis (1–10 cm) called a bubo, possible sepsis | Streptomycin, 30 mg/kg/d IM divided b.i.d. 10–14 d, or gentamicin, 5 mg/kg IV × 10–14 d | Doxycycline, 100 mg PO b.i.d. × 7 d, or ciprofloxacin, 500 mg PO b.i.d. × 7 d |
| Septicemia (can be primary or secondary) | Fever, chills, dyspnea, hypotension, purpura | Gangrene of nose and extremities, disseminated intravascular coagulation, death | ||||
| Pneumonic | 1–6 d | Fever, chills, productive cough, dyspnea, hypoxia, nausea and vomiting | Sepsis | |||
| Tularemia (Francisella tularensis; aerobic, gram-negative coccobacilli) | Ulceroglandular | Patients with any type may present with fever, chills, headache, myalgia, malaise, maculopapular rash; all types can spread hematogenously | Papule (inoculation site) → pustule → tender ulcer (yellow exudates, black base), painful regional lymphadenopathy | Streptomycin, 10 mg/kg/d IM divided b.i.d. × 10 d, or gentamicin, 5 mg/kg IV × 10 d | Doxycycline, 100 mg PO b.i.d. × 14 d, or ciprofloxacin, 500 mg PO b.i.d. × 14 d | |
| Glandular | Same as above except without ulcer | |||||
| Occuloglandular | Painful conjunctivitis, lymphadenopathy, ulcerations on palpebral conjunctiva | |||||
| Oropharyngeal | Exudative pharyngotonsillitis, lymphadenopathy | |||||
| Pneumonic | Pharyngitis, bronchiolitis, hilar lymphadenopathy, pneumonia, pulmonary failure, death | |||||
| Typhoidal | Sepsis | |||||
| Brucellosis (pleomorphic gram-negative coccobacilli) | 1–3 wk | Fever, chills, malaise, myalgias | May afflict a variety of organs or organ systems | Rifampin, 600 mg/d PO, plus doxycycline, 200 mg/d PO × 6 wk | Same as treatment course, but may be shortened to 3 wk | |
| Q fever (Coxiella burnetii) | Can be acute or indolent in its course | 5–30 d | Fever, chills, headache, malaise, myalgia, anorexia | May afflict a variety of organs or organ systems. Endocarditis and gastrointestinal symptoms are common | Tetracycline, 500 mg PO q 6 h × 5–7 d, or doxycycline, 100 mg PO b.i.d. × 5–7 d | Same as treatment course |
| Glanders and melioidosis (Burkholderia spp; gram-negative bacillus) | Localized | 1–2 wk | Wound contamination, cellulitis, lymphadenopathy lymphangitis | Sepsis can result with all modes of infection; death from sepsis occurs in 7–10 d | Local disease: amoxicillin–clavulanate, 60 mg/kg/d divided t.i.d. × 60 d. Severe disease: ceftazidime, 120 mg/kg/d divided t.i.d., plus trimethoprim–sulfamethoxazole, 8 mg/kg/d divided q.i.d. × 2 wk, followed by prolonged oral therapy | Trimethoprim–sulfamethoxazole (160/800 mg) PO b.i.d. × 14 d |
| Pulmonary | Fever, chills, cough, dyspnea | |||||
| Septicemic | Fever, chills, malaise, abscesses, headache, pustular rash | |||||
Bacillus anthracis is a gram-positive, sporulating rod. Anthrax infection occurs naturally after contact with contaminated animals or contaminated animal products. A biologic attack would likely involve the aerosol release of anthrax spores. Clinically, the disease occurs in three forms: inhalational, gastrointestinal, and cutaneous.
Inhalational anthrax is the form of disease most likely expected after a terrorist attack. After spores are inhaled, an incubation period occurs, usually lasting 1–7 days. However, incubation periods of up to 60 days have been observed. Initially, nonspecific symptoms of fever, cough, headache, chills, vomiting, dyspnea, chest pain, abdominal pain, and weakness occur. This stage may last from a few hours to a few days. Following these nonspecific symptoms, a transient period of improvement may be seen. When the second stage of disease is reached, high fever, diaphoresis, cyanosis, hypotension, lymphadenopathy, shock, and death will occur. Often, death will occur within hours once the second stage is reached. The average time from onset of symptoms to death is 3 days. Once the initial symptoms of inhalational anthrax develop, the overall mortality rate may be as high as 95%. Early diagnosis of anthrax infection and rapid initiation of therapy may improve survival.
Gastrointestinal anthrax occurs when spores are ingested into the digestive tract. Two forms of the disease occur: oropharyngeal and abdominal. Oropharyngeal disease occurs when spores are deposited in the upper gastrointestinal tract. An oral or esophageal ulcer develops followed by regional lymphadenopathy and eventual sepsis. In abdominal anthrax, the spores are deposited in the lower gastrointestinal tract. Symptoms include nausea, vomiting, bloody diarrhea, and the development of an acute abdomen with sepsis. Mortality rates for gastrointestinal anthrax are in excess of 50%.
Cutaneous anthrax is the most common naturally occurring form of the disease. It occurs when spores come in contact with open skin lesions. This usually occurs on the arms, hands, and face. Following exposure, a small, often pruritic, papule will develop. Eventually, this papule will turn into a small ulcer over 2 days, then progress to a small vesicle, and ultimately to a painless black eschar with surrounding edema. Then, over a period of 1–2 weeks, the eschar will dry and fall off. Regional lymphadenitis or lymphadenopathy may also occur. In some case, secondary sepsis may develop. Without treatment, cutaneous anthrax has a mortality rate of 20%; however, the mortality rate drops to 1% with treatment.
Anthrax meningitis can occur as a complication of any other form of anthrax. Symptoms include headache and meningismus. Anthrax meningitis carries a mortality rate of nearly 100%.
Multiple laboratory studies can be used to identify anthrax. In fulminant cases, the organism may be seen on routine Gram stain. Blood cultures, wound cultures, and nasal cultures may be obtained. Given the lack of an infiltrate, sputum cultures are rarely useful. Often Bacillus spp. are thought to be the contaminant; therefore, notify laboratory personnel of possible anthrax. Confirmatory enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) tests are available at some national reference laboratories. Patients with inhalational anthrax will display a wide mediastinum on chest x-ray without infiltrate.
Because anthrax has a rapid and fulminant course, do not delay treatment while awaiting confirmatory tests. Delaying empiric treatment for even hours may significantly increase mortality.
Most naturally occurring strains of anthrax are sensitive to penicillin. Some strains, however, are penicillin resistant. Weapons-grade anthrax is likely to be penicillin resistant. As a result, the first-line therapy is now ciprofloxacin; doxycycline is an acceptable alternative (see Table 3–1). Treatment should continue for 60 days. If cultures were obtained, later sensitivity testing may direct antibiotic use.
Patients may require intensive medical support such as airway management, hemodynamic support, and various measures to manage multisystem organ failure.
Individuals thought to be at high risk for anthrax exposure should receive treatment as though infection has occurred. Later, laboratory analysis may allow discontinuation of therapy. An anthrax vaccination is available and requires injections at 0, 2, and 4 weeks, followed by injections at 6, 12, and 18 months. An annual booster is also required. If a combination of vaccination and antibiotics is used during treatment, the course of antibiotics may be shortened to 30 days.
No data indicate that anthrax is spread via person-to-person contact. Use standard precautions during patient care activities (Table 3–2).
| Protection Level | Required Equipment |
|---|---|
| Standard precautions | Universal precautions; hand washing; protective gloves; gown, mask, eye protection, if splash risk exists |
| Droplet precautions | Same as standard precautions, except add surgical or Hepa filter mask |
| Airborne precautions | Same as standard precautions, except add negative pressure room, strict isolation; Hepa filter mask required |
Yersinia pestis is a nonmotile, gram-negative bacillus. Plague occurs naturally after the bite of an infected arthropod vector. Biologic attack would most likely involve the aerosolized release of Y. pestis. Plague occurs in three clinical forms: bubonic plague, septicemic plague, and pneumonic plague.
Bubonic plague is the most common naturally occurring form of the disease. Infection begins with the bite of a contaminated flea. A latent period then occurs and may last up to 1 week, followed by fevers, chills, and weakness. Eventually, the organism will migrate to the regional lymph nodes where it causes destruction and necrosis. A swollen and tender lymph node called a bubo will develop, which ranges from 1 to 10 cm. Some patients may develop secondary sepsis. Without treatment, bubonic plague has an estimated mortality rate of 50%; however, with antibiotic therapy the mortality rate falls to 10%.
Septicemic plague may occur either as a complication of other forms of plague or as a primary entity. Symptoms include fever, dyspnea, hypotension, and purpuric skin lesions. Gangrene of the nose and extremities may occur, hence the name “black death.” Complications of disseminated intravascular coagulation may also be evident. Without treatment, septicemic plague has an estimated mortality rate of 100%; however, with antibiotic therapy the mortality rate falls to 40%.
Pneumonic plague may occur either as a complication of other forms of plague or as a primary entity. It is the most likely form of the disease to result from a terrorist attack. A latent period of 1–6 days following exposure is likely. Patients will then develop signs and symptoms of severe pulmonary infection including fever, cough, dyspnea, hypoxia, and sputum production. Gastrointestinal symptoms of nausea, vomiting, and diarrhea may also occur. Pneumonic plague has an estimated mortality rate of 100% if antibiotic therapy is not begun within 24 hours.
Y. pestis can be identified by several different staining techniques, including routine Gram, Wright, Giemsa, and Wayson stains. Blood cultures, sputum cultures, and cultures of lymph node aspirates may be useful. Specialized rapid confirmatory tests are available at some laboratories. In patients with pneumonic plague, chest x-ray will display a patchy or confluent infiltrate.
Plague has a rapid disease progression, and any delay in empiric treatment will cause significant increases in mortality.
Streptomycin or gentamicin is the drug of choice for the treatment of plague (see Table 3–1). Alternative antibiotics include doxycycline, ciprofloxacin, and chloramphenicol.
Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
Patients in a community experiencing a pneumonic plague epidemic should receive antibiotic therapy if they develop a cough or a fever above 38.5°C (101.2°F). Any person who has been in close contact with an individual with plague should receive a 7-day course of antibiotics.
Pneumonic plague can be spread from person to person by aerosol droplets. Use droplet precautions, and either the patient or the caregivers should wear masks (see Table 3–2). Once the patient has received 48 hours of antibiotics and has improved clinically, standard precautions may be used.
Francisella tularensis is a nonmotile, aerobic, gram-negative coccobacillus. Two strains of tularemia are known to exist. F. tularensis biovar tularensis is considered highly virulent, whereas F. tularensis biovar palaearctiais more benign. Tularemia occurs naturally after the bite of an infected arthropod vector or after exposure to contaminated animal products. Biologic attack would most likely involve the release of aerosolized F. tularensis. Tularemia displays multiple clinical forms including ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal forms. The form of disease depends on the site and type of inoculation.
Patients with any form of tularemia may present with the abrupt onset of fever, chills, headache, malaise, and myalgias. Often a maculopapular rash is seen.
Ulceroglandular tularemia usually occurs after handling infected animals or after the bite of an infected arthropod vector. At the inoculation site, a papule will form that will eventually become a pustule and then a tender ulcer. The ulcer may have a yellow exudate and will slowly develop a black base. Regional lymph nodes will become swollen and painful.
Glandular tularemia displays signs and symptoms similar to ulceroglandular tularemia, except that no ulcer formation is noted.
After ocular inoculation, a painful conjunctivitis will develop with regional lymphadenopathy. Lymphadenopathy may involve the cervical, submandibular, or preauricular chains. In some cases, ulcerations occur on the palpebral conjunctiva.
After inoculation of the pharynx, an exudative pharyngotonsillitis will develop with cervical lymphadenopathy.
Pneumonic tularemia occurs after inhalation of F. tularensis or following secondary spread from other infectious foci. A terrorist attack will most likely cause this form of disease. The findings of pulmonary involvement are variable and include pharyngitis, bronchiolitis, hilar lymphadenitis, and pneumonia. Early in the course of disease, systemic symptoms may predominate over pulmonary symptoms. In some cases, however, pulmonary disease progresses rapidly to pneumonia, pulmonary failure, and death.
In this form of tularemia, systemic signs and symptoms of disease are present without a clear infectious site. Signs and symptoms include fever, chills, headache, malaise, and myalgias.
Any form of tularemia may be complicated by hematogenous spread leading to pneumonia, meningitis, or sepsis. The overall mortality rates for untreated tularemia range from 10% to 30%; however, with antibiotic therapy, mortality rates drop to less than 1%.
F. tularensis requires special growth media. Notify laboratory personnel of a possible tularemia specimen so that proper plating can be performed. Cultures may be obtained from sputum, pharyngeal, or blood specimens. Specialized ELISA and PCR confirmatory tests are also available at some reference laboratories. In the case of pneumonic tularemia, chest x-ray may demonstrate peribronchial infiltrates, bronchopneumonia, or pleural effusions.
Streptomycin and gentamicin are considered the drugs of choice for the treatment of tularemia (see Table 3–1). Ciprofloxacin has also displayed efficacy against tularemia. Second-line agents such as tetracycline and chloramphenicol may be used, but these agents are associated with higher rates of treatment failure. A 10-day course of antibiotics should be used. For second-line agents, a 14-day course should be used.
Rarely, patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
Some data suggest that a 14-day course of antibiotics begun during the incubation period may prevent disease. Antibiotic choices are the same as for treatment. A live attenuated vaccine for tularemia also exists and is often used for at-risk laboratory workers. Vaccination decreases the rate of inhalational tularemia but does not confer complete protection. Given tularemia’s short incubation period, and the incomplete protection of the vaccine, postexposure vaccination is not recommended.
Significant person-to-person transmission of tularemia does not occur. Standard precautions are sufficient during patient care activities (see Table 3–2).
Brucellae are small aerobic, gram-negative, pleomorphic coccobacilli. Many Brucella spp. occur naturally; however, only four species are infectious to humans. Each species typically infects a particular host organism, and human infection follows contact with contaminated animal material. The Brucella spp. that are infectious to humans are B. melitensis (found in goats), B. suis (found in swine), B. abortus (found in cattle), and B. canis (found in dogs). B. suis has been weaponized in the past.
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